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Biomedical subjects

A M Lerner

Publications and source records attributed to A M Lerner.

At least 37 records · Page 2Linked to original sources

Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin.

254 patients with serious gram-negative bacillary infections were enrolled into a multicentre, randomised, blind clinical trial and treated with tobramycin-ticarcillin or netilmicin-ticarcillin. The two treatment groups were similar as to sex, age, and weight. The mean daily dose of netilmicin (237 mg) was higher than that of tobramycin (211 mg), p less than 0.01, but the mean duration of therapy was longer with tobramycin (9.4 days versus 8.7 days), p less than 0.01. The netilmicin cohort also had more serious underlying diseases, p less than 0.028. Clinical (tobramycin, 93% and netilmicin, 91%) and bacteriological responses (tobramycin, 87% and netilmicin, 89%) were similar. 84 tobramycin and 73 netilmicin patients had serial audiograms. Eighth nerve deficits developed in 10 (12%) tobramycin and two (3%) netilmicin patients, p = 0.037. Drug-related renal dysfunction developed in 5 (4%) of 114 tobramycin patients whose renal function was monitored and in 1 (1%) of 116 netilmicin patients, p = 0.12.

Anti-Bacterial Agents↗

Disseminated neonatal echovirus 11 disease following antenatal maternal infection with a virus-positive cervix and virus-negative gastrointestinal tract.

An infant girl was born apparently well one week after her mother had had a mild illness with chills, fever, and diarrhea. On the third day of life, the infant became ill and died four days later with necrotizing hepatitis. On the same day, echovirus type 11 was recovered from the throat, rectum, and buffy coat of the infant and from the cervix of the mother. At this time, the mother had an IgM neutralizing antibody titer to echovirus type 11 and 1:128, but no IgG antibodies. The infant had no echovirus type 11 antibodies. The virus was also isolated from the baby's liver and adrenal at autopsy. These findings raise the possibility of enterovirus infection at delivery from a contaminated cervix.

Adult↗

Alterations in coxsackievirus B4 heart muscle disease in ICR Swiss mice by anti-thymocyte serum.

Coxsackievirus B4 (CB4) infection in infant ICR Swiss mice induces synchronous peaks in both virus titres and pathologic changes in the heart. Among surviving mice, transmural necrosis is followed by fibrosis and ventricular aneurysm. Rabbit antimouse thymocyte serum (ATS) was given before CB4 infection to determine the effects of thymus-dependent functions upon the course of disease. The mortality in ATS-treated mice was 75.9% (65 of 83 mice died) compared to 21.3% (16 of 75 mice died) in normal rabbit serum-treated controls. Pathologic studies showed that ATS-treated mice had more extensive myofibre necrosis and subsequent mineralization, but during the first 10 days of infection, leukocytic infiltration was decreased. Splenic follicles were not present until the 17th day after infection in this treated group. Serum CB4-neutralizing antibodies were similar in mice from the group treated with ATS and normal rabbit serum. These findings indicate that ATS-suppressible functions contribute importantly to virus elimination, perhaps by an increase in macrophage phagocytosis of CB4.

Animals↗

Theophylline-induced seizures: clinical and pathophysiologic aspects.

The clinical features and management of theophylline-induced seizures are not well appreciated in spite of their unique aspects. These seizures tend to occur in neurologically intact patients and leave no or only minor neurologic sequelae if controlled early. They begin with focal motor seizures with or without secondary generalization and are followed by stupor or coma. They are responsive only to adjustment of theophylline dosage. Should the motor phenomenon persist, it takes the form of epilepsia partialis continua. Extensive workup for a structural brain lesion may be unrewarding. The electroencephalogram typically shows periodic lateralized epileptiform discharges, which may provide a diagnostic clue.

Aged↗

Agranulocytosis associated with chronic oral administration of cloxacillin for suppression of staphylococcal osteomyelitis.

Oral cloxacillin was used for chronic suppression of a 59-year-old woman with staphylococcal osteomyelitis. She received 380.5 gm of cloxacillin over 263 consecutive days. Severe agranulocytosis followed, reverting rapidly to normal with cessation of drug. The absence of signs of an allergic reactions such as rash, fever, or eosinophilia suggests that cloxacillin, like other semisynthetic penicillins, may exert a direct bone marrow toxicity.

Agranulocytosis↗

Pharmacokinetics of interferon in blood, cerebrospinal fluid, and brain after administration of modified polyriboinosinic-polyribocytidylic acid and amphotericin B.

Polyriboinosinic-polyribocytidylic acid (with a sedimentation coefficient of 9S) prepared in a complex with poly-L-lysine and carboxymethylcellulose (poly ICLC) was given intravenously to rabbits in a priming technique with two infusions 4 hr apart; and with low-dose amphotericin B (AmB, 0.5 mg) to trace the transfer of interferon (IFN) in serum to cerebrospinal fluid (CSF) and brain. Peak titers of IFN in serum were at 4 hr, but peak titers of IFN in CSF and brain occurred at 8 hr. At 4 hr, CSF IFN was 0.6%-2.7% of serum titers but at 8 hr had increased to 11.7%-51.1%. IFN was uniformly distributed to all areas of the brain and spinal cord at 8 hr. Titers of IFN in the brain were independent of CSF values, and varied from 5.9%-44.1% of the serum titers. When two injections of poly ICLC were given 4 hr apart, IFN titers in serum, CSF, and brain were significantly raised. Poly ICLC together with AmB increased serum IFN.

Amphotericin B↗

Topical polyriboinosinic-polyribocytidylic acid complex in the treatment of recurrent genital herpes.

Polyriboinosinic-polyribocytidylic acid complexed with poly-l-lysine and carboxymethylcellulose [poly(ICLC)] is a potent interferon inducer when given parenterally to humans. Topical application in animal models has shown beneficial antiviral and clinical effects. In a randomized, double-blinded, placebo-controlled trial of topical poly(ICLC) in recurrent genital herpes simplex virus infection, five clinical and two virological parameters were followed. Fifty-seven men and women, with 78 recurrences of genital herpes, were stratified by sex. No clinical or antiviral differences between poly(ICLC) and placebo groups in either stratum were found. Further analysis of male subgroups by age and size of lesions showed no changes in the rapidity of healing or viral shedding.

Administration, Topical↗

A mouse model of transmural myocardial necrosis due to coxsackievirus B4: observations over 12 months.

The course of coxsackievirus B4 necrotizing myocarditis was studied over a 12-month period in 712 ICR Swiss mice inoculated at less than 48 h of age. Affected animals were sacrificed at intervals until 1 year. Microscopically, focal myocardial necrosis, which was often transmural in extent with mixed inflammatory exudate, and subsequent fibrous replacement were induced in 75% of the examined animals. The left ventricle (63 of 69 subjects, 91.3%), interventricular septum (39 of 69 subjects, 56.5%) and right ventricle (26 of 69 subjects, 37.7%) were most frequently involved. Thinning of the ventricular wall and grossly apparent localized ventricular bulges (aneurysms) were seen in 22 subjects (the left ventricle 16 times, the right ventricle 5 times, and the interventricular septum 5 times). Coronary arteries were normal in all instances.

Animals↗

Pseudomonas cepacia peritonitis associated with contamination of automatic peritoneal dialysis machines.

During a 3-month period, Pseudomonas cepacia was recovered from the peritoneal fluid of 10 patients having chronic dialysis therapy at a peritoneal dialysis center. Six patients developed clinical evidence of peritonitis; one patient developed septicemia. Epidemiologic studies showed that dialysis on specific peritoneal dialysis machines was associated with an increased risk of infection. Laboratory investigation showed contamination of two machines with P. cepacia. Inadequacies in the cleaning and disinfection practices of the automatic peritoneal dialysis machines were identified. Cross-contamination between machines probably occurred through the peritoneal fluid discharge from infected patients during dialysis. Also, the intermittent 2-hour exposure of the machine to 2% formaldehyde may have been inadequate. P. cepacia has not been isolated from the peritoneal fluid of any peritoneal dialysis patient after machine cleaning and disinfection practices were altered.

Adult↗

A mouse model of dilated-type cardiomyopathy due to coxsackievirus B3.

Myocardial scarring was induced in 111 mice (group 3) inoculated at 14 days of age with coxsackievirus B3 and forced to swim for 30 min daily during the initial nine days of infection. The animals were observed until age 15 months. Control animals included mice infected but not forced to swim (group 2), neither infected nor forced to swim (group 1), and not infected but forced to swim (group 4). The cumulative mortality was 45% among mice in group 3 but was significantly lower in the control animals. At 15 months, mice in group 3 showed heavy deposits of calcium in the injured myocardium, atrial hypertrophy with thrombi, and myocardial fiber disintegration with replacement by fibrous scar. Mononuclear infiltration was no longer present. Pathologic changes were concentrated in the left ventricle, interventricular septum, and atrioventricular junction. Titers of type-specific neutralizing antibodies had declined to one-fifth the level present at one month. These findings represent a model of dilated-type cardiomyopathy.

Animals↗

Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis.

In a single line of human foreskin fibroblasts, minimum inhibitory concentrations (MICs) and the minimum intracellular virus inactivation concentrations (MIICs) of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were assayed for a number of recent isolates of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV). (The term MIIC is used here to describe the selective qualitative intracellular inhibition of the virus inoculum in the primary tissue cultures. The inoculum is not recoverable in subcultures free of antiviral agent.) MICs and MIICs of each of the antiviral agents were readily obtained for each strain of HSV-1, HSV-2, and VZV tested, but all seven strains of CMV tested were much more resistant. At the endpoint, there was little variation in the MICs or MIICs among strans of the same virus. Final MIC results for HSV-1 and HSV-2 were complete after 3 days of incubation; CMV and VZV results required as long as 6 days. The MIC for each herpesvirus increased with incubation, but at the endpoint the MIC and MIIC were approximately equal. VZV was most susceptible to each drug, followed by HSV-1 and HSV-2. The latter two viruses were quite similar. There was no difference in antiviral susceptibilities among any of the strains of HSV-1, HSV-2, VZV, or CMV tested. The toxicities of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were simultaneously compared by using both microscopic cytotoxicity and inhibition of uptakes of [14C]thymidine into cellular deoxyribonucleic acid and of 14C-labeled amino acids into protein. The selective inhibition of each antiviral agent against viral and cellular deoxyribonucleic acid polymerases was confirmed. Simultaneous assays of antiviral and anticellular activities of antiviral agents may be useful in projecting further in vivo experiments.

Antiviral Agents↗